The objectives of this project entitled "Polyene Marcolides - Pharmacology and Toxicology" are: (1) the preparation by fermentation of a variety of different commercially unavailable polyene macrolides representative of different structural groups such as the tetraenes, the pentaenes, the hexaenes, and the heptaenes; (2) the isolation and purification of individual polyene macrolide components from complex fermentation products; (3) the preparation of radioactive polyene macrolides by fermentation procedures employing radiocarbon and tritium labelled biochemical precursors; (4) the preparation of biologically- active polyene macrolide derivatives including the water soluble salts of the methyl ester derivatives, etc.; (5) the preparation of radioactive derivatives by chemical synthesis; (6) the study in small laboratory animals of the metabolic fate and the pharmacological effects of various pure polyene macrolides and their derivatives by oral and parenteral routes of administration; (7) the study of the nature of the acute and chronic toxicities of these compounds in small laboratory animals; (8) the study of the in vitro and in vivo chemotherapeutic efficacy of these compounds based on the knowledge acquired from the above pharmacological and toxicological studies; (9) the availability of polyene macrolides and their synthetic derivatives, both unlabeled and carbon-14 and tritium labeled, for NIH authorized pharmacological, biochemical, and chemotherapeutic studies by other investigators.